Research on oxygen toxicity at the cellular level Final report, 15 Apr. 1965 - 15 Jun. 1966

Oxygen toxicity at cellular level in manned spacecraf

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

To estimate risk of NEC for ELBW infants as a function of preterm formula and maternal milk (MM) intake and calculate the impact of suboptimal feeding on NEC incidence and costs

Pirfenidone in patients with idiopathic pulmonary fibrosis (CAPACITY): two randomised trials.

BACKGROUND: Idiopathic pulmonary fibrosis is a progressive and fatal lung disease with inevitable loss of lung function. The CAPACITY programme (studies 004 and 006) was designed to confirm the results of a phase 2 study that suggested that pirfenidone, a novel antifibrotic and anti-inflammatory drug, reduces deterioration in lung function in patients with idiopathic pulmonary fibrosis. METHODS: In two concurrent trials (004 and 006), patients (aged 40-80 years) with idiopathic pulmonary fibrosis were randomly assigned to oral pirfenidone or placebo for a minimum of 72 weeks in 110 centres in Australia, Europe, and North America. In study 004, patients were assigned in a 2:1:2 ratio to pirfenidone 2403 mg/day, pirfenidone 1197 mg/day, or placebo; in study 006, patients were assigned in a 1:1 ratio to pirfenidone 2403 mg/day or placebo. The randomisation code (permuted block design) was computer generated and stratified by region. All study personnel were masked to treatment group assignment until after final database lock. Treatments were administered orally, 801 mg or 399 mg three times a day. The primary endpoint was change in percentage predicted forced vital capacity (FVC) at week 72. Analysis was by intention to treat. The studies are registered with ClinicalTrials.gov, numbers NCT00287729 and NCT00287716. FINDINGS: In study 004, 174 of 435 patients were assigned to pirfenidone 2403 mg/day, 87 to pirfenidone 1197 mg/day, and 174 to placebo. In study 006, 171 of 344 patients were assigned to pirfenidone 2403 mg/day, and 173 to placebo. All patients in both studies were analysed. In study 004, pirfenidone reduced decline in FVC (p=0·001). Mean FVC change at week 72 was -8·0% (SD 16·5) in the pirfenidone 2403 mg/day group and -12·4% (18·5) in the placebo group (difference 4·4%, 95% CI 0·7 to 9·1); 35 (20%) of 174 versus 60 (35%) of 174 patients, respectively, had a decline of at least 10%. A significant treatment effect was noted at all timepoints from week 24 and in an analysis over all study timepoints (p=0·0007). Mean change in percentage FVC in the pirfenidone 1197 mg/day group was intermediate to that in the pirfenidone 2403 mg/day and placebo groups. In study 006, the difference between groups in FVC change at week 72 was not significant (p=0·501). Mean change in FVC at week 72 was -9·0% (SD 19·6) in the pirfenidone group and -9·6% (19·1) in the placebo group, and the difference between groups in predicted FVC change at week 72 was not significant (0·6%, -3·5 to 4·7); however, a consistent pirfenidone effect was apparent until week 48 (p=0·005) and in an analysis of all study timepoints (p=0·007). Patients in the pirfenidone 2403 mg/day group had higher incidences of nausea (125 [36%] of 345 vs 60 [17%] of 347), dyspepsia (66 [19%] vs 26 [7%]), vomiting (47 [14%] vs 15 [4%]), anorexia (37 [11%] vs 13 [4%]), photosensitivity (42 [12%] vs 6 [2%]), rash (111 [32%] vs 40 [12%]), and dizziness (63 [18%] vs 35 [10%]) than did those in the placebo group. Fewer overall deaths (19 [6%] vs 29 [8%]) and fewer deaths related to idiopathic pulmonary fibrosis (12 [3%] vs 25 [7%]) occurred in the pirfenidone 2403 mg/day groups than in the placebo groups. INTERPRETATION: The data show pirfenidone has a favourable benefit risk profile and represents an appropriate treatment option for patients with idiopathic pulmonary fibrosis

Survey of Borreliae in ticks, canines, and white-tailed deer from Arkansas, U.S.A.

<p>Abstract</p> <p>Background</p> <p>In the Eastern and Upper Midwestern regions of North America, <it>Ixodes scapularis</it> (L.) is the most abundant tick species encountered by humans and the primary vector of <it>B. burgdorferi,</it> whereas in the southeastern region <it>Amblyomma americanum</it> (Say) is the most abundant tick species encountered by humans but cannot transmit <it>B. burgdorferi.</it> Surveys of Borreliae in ticks have been conducted in the southeastern United States and often these surveys identify <it>B. lonestari</it> as the primary <it>Borrelia</it> species, surveys have not included Arkansas ticks, canines, or white-tailed deer and <it>B. lonestari</it> is not considered pathogenic. The objective of this study was to identify <it>Borrelia</it> species within Arkansas by screening ticks (n = 2123), canines (n = 173), and white-tailed deer (n = 228) to determine the identity and locations of Borreliae endemic to Arkansas using PCR amplification of the flagellin (<it>flaB)</it> gene.</p> <p>Methods</p> <p>Field collected ticks from canines and from hunter-killed white-tailed were identified to species and life stage. After which, ticks and their hosts were screened for the presence of <it>Borrelia</it> using PCR to amplify the <it>flaB</it> gene. A subset of the positive samples was confirmed with bidirectional sequencing.</p> <p>Results</p> <p>In total 53 (21.2%) white-tailed deer, ten (6%) canines, and 583 (27.5%) Ixodid ticks (252 <it>Ixodes scapularis</it>, 161 <it>A. americanum</it>, 88 <it>Rhipicephalus sanguineus</it>, 50 <it>Amblyomma maculatum,</it> 19 <it>Dermacentor variabilis,</it> and 13 unidentified <it>Amblyomma</it> species) produced a <it>Borrelia flaB</it> amplicon. Of the positive ticks, 324 (22.7%) were collected from canines (151 <it>A. americanum,</it> 78 <it>R. sanguineus</it>, 43 <it>I. scapularis,</it> 26 <it>A. maculatum,</it> 18 <it>D. variabilis</it>, and 8 <it>Amblyomma</it> species) and 259 (37.2%) were collected from white-tailed deer (209 <it>I. scapularis,</it> 24 <it>A. maculatum,</it> 10 <it>A. americanum,</it> 10 <it>R. sanguineus</it>, 1 <it>D. variabilis</it>, and 5 <it>Amblyomma</it> species). None of the larvae were PCR positive. A majority of the <it>flaB</it> amplicons were homologous with <it>B. lonestari</it> sequences: 281 of the 296 sequenced ticks, 3 canines, and 27 deer. Only 22 deer, 7 canines, and 15 tick <it>flaB</it> amplicons (12 <it>I. scapularis</it>, 2 <it>A. maculatum</it>, and 1 <it>Amblyomma</it> species) were homologous with <it>B. burgdorferi</it> sequences.</p> <p>Conclusions</p> <p>Data from this study identified multiple Borreliae genotypes in Arkansas ticks, canines and deer including <it>B. burgdorferi</it> and <it>B. lonestari;</it> however, <it>B. lonestari</it> was significantly more prevalent in the tick population than <it>B. burgdorferi</it>. Results from this study suggest that the majority of tick-borne diseases in Arkansas are not <it>B. burgdorferi.</it></p

Aspirin and mortality from coronary bypass surgery

BACKGROUND: There is no therapy known to reduce the risk of complications or death after coronary bypass surgery. Because platelet activation constitutes a pivotal mechanism for injury in patients with atherosclerosis, we assessed whether early treatment with aspirin could improve survival after coronary bypass surgery. METHODS: At 70 centers in 17 countries, we prospectively studied 5065 patients undergoing coronary bypass surgery, of whom 5022 survived the first 48 hours after surgery. We gathered data on 7500 variables per patient and adjudicated outcomes centrally. The primary focus was to discern the relation between early aspirin use and fatal and nonfatal outcomes. RESULTS: During hospitalization, 164 patients died (3.2 percent), and 812 others (16.0 percent) had nonfatal cardiac, cerebral, renal, or gastrointestinal ischemic complications. Among patients who received aspirin (up to 650 mg) within 48 hours after revascularization, subsequent mortality was 1.3 percent (40 of 2999 patients), as compared with 4.0 percent among those who did not receive aspirin during this period (81 of 2023, P<0.001). Aspirin therapy was associated with a 48 percent reduction in the incidence of myocardial infarction (2.8 percent vs. 5.4 percent, P<0.001), a 50 percent reduction in the incidence of stroke (1.3 percent vs. 2.6 percent, P=0.01), a 74 percent reduction in the incidence of renal failure (0.9 percent vs. 3.4 percent, P<0.001), and a 62 percent reduction in the incidence of bowel infarction (0.3 percent vs. 0.8 percent, P=0.01). Multivariate analysis showed that no other factor or medication was independently associated with reduced rates of these outcomes and that the risk of hemorrhage, gastritis, infection, or impaired wound healing was not increased with aspirin use (odds ratio for these adverse events, 0.63; 95 percent confidence interval, 0.54 to 0.74). CONCLUSIONS: Early use of aspirin after coronary bypass surgery is safe and is associated with a reduced risk of death and ischemic complications involving the heart, brain, kidneys, and gastrointestinal tract

Impact of Optimized Breastfeeding on the Costs of Necrotizing Enterocolitis in Extremely Low Birthweight Infants

ObjectiveTo estimate risk of necrotizing enterocolitis (NEC) for extremely low birth weight (ELBW) infants as a function of preterm formula (PF) and maternal milk intake and calculate the impact of suboptimal feeding on the incidence and costs of NEC.Study designWe used aORs derived from the Glutamine Trial to perform Monte Carlo simulation of a cohort of&nbsp;ELBW infants under current suboptimal feeding practices, compared with a theoretical cohort in which 90% of infants received at least 98% human milk.ResultsNEC incidence among infants receiving ≥98% human milk was 1.3%; 11.1% among infants fed only PF; and 8.2% among infants fed a mixed diet (P&nbsp;=&nbsp;.002). In adjusted models, compared with infants fed predominantly human milk, we found an increased risk of NEC associated with exclusive PF (aOR&nbsp;=&nbsp;12.1, 95% CI 1.5, 94.2), or a mixed diet (aOR 8.7, 95% CI 1.2-65.2). In Monte Carlo simulation, current feeding of ELBW infants was associated with 928 excess NEC cases and 121 excess deaths annually, compared with a model in which 90% of infants received ≥98% human milk. These models estimated an annual cost of suboptimal feeding of ELBW infants of $27.1 million (CI$24 million, $30.4 million) in direct medical costs,$563 655 (CI $476 191,$599 069) in indirect nonmedical costs, and $1.5 billion (CI$1.3 billion, $1.6 billion) in cost attributable to premature death.ConclusionsAmong ELBW infants, not being fed predominantly human milk is associated with an increased risk of NEC. Efforts to support milk production by mothers of ELBW infants may prevent infant deaths and reduce costs